Tumors larger than microscopic size have inadequate and abnormal vasculature. As a consequence, areas of tumors that are more than a few tens of microns from a capillary are generally hypoxic. Cells in such hypoxic areas of tumors either die or convert to anaerobic metabolism which results in their excreting lactic acid. Because of the poor circulation in tumors, that excreted lactic acid builds up in the interstitial space in hypoxic areas of tumors.
There are two important consequences of this process.
1) While the pH in the interstitial space in normal tissues ranges from about 7.2 to 7.5, the interstitial space in hypoxic areas of tumors is acidic, with pH ranging from as low as about 6.0 in areas most distant from capillaries, up to about 7.0 closer to capillaries.2) While tumor cells in close proximity to capillaries are characterized by high metabolic rates and fast cell division, the tumor cells in acidic areas more distant from capillaries have lower metabolic rates and are slower-dividing or non-dividing. The slow-dividing and non-dividing tumor cells are referred to as quiescent.
Conventional cancer therapies, including chemotherapy and radiation, are generally fairly effective in killing fast-dividing cells, but because conventional cancer therapies are explicitly selected on the basis of their ability to spare slow-dividing and non-dividing cells typical of most normal tissues, said cancer therapies are also relatively ineffective against slow-dividing and non-dividing quiescent tumor cells. As a consequence, cancer treatments typically kill predominantly the fast-dividing cells of a tumor, while sparing the quiescent cells of the tumor. The initial killing of the fast-dividing tumor cells causes the tumor to go into remission. After those killed cells have been disposed of by the body's normal cleanup processes, all too often the treatment-resistant quiescent cancer cells in the hypoxic areas of the tumor slowly regain access to adequate oxygen, nutrients, and waste disposal, thus allowing them to revert to high metabolic rate and fast cell division. Reversion of the previously-quiescent cancer cells manifests as the dreaded relapse that so often kills cancer patients.
To achieve more effective treatment of tumors it is desirable to have a means for sensitive detection of quiescent cancer cells in virtually all tumors. Also desired is to have a broadly effective means for selectively killing those treatment-resistant quiescent cancer cells without concomitant killing of cells in normal tissues.